Treatment Of Cervical Intraepithelial Neoplasia Research Articles

Evidence-based medicine: Indole-3-carbinol and resveratrol in human papillomavirus-associated conditions

Of all types of cancer in the female reproductive system, cervical cancer has the greatest social significance due to its impact on young patients, often even those who have not yet completed their reproductive function, and it is the third leading cause of cancer-related death. Considering the lack of etiological therapy for human papillomavirus and associated diseases, the high demand for effective methods of medical therapeutic support, and the absence of a gold standard treatment apart from destructive and excisional methods, it seems reasonable to consider the use of nutrients with anticancer effects in the treatment of low-grade cervical intraepithelial neoplasia both as an addition to the watchful waiting strategy and in the use of ablative treatment methods, as well as their adjuvant appointment in the case of obligatory precancer. Based on domestic and foreign literature sources from electronic databases such as PubMed, CyberLeninka, and Elibrary, this review presents data on the use of trans-resveratrol and indole-3-carbinol in HPV-associated diseases. The combination of two mutually complementary anticancer antioxidants – indole-3-carbinol, which primarily has antiproliferative effects, and trans-resveratrol, which restores cellular apoptosis mechanisms, comprehensively affects the pathogenetic mechanisms of the virus-induced pathological process: it has been proven to reduce the expression of oncogenes E6 and E7, increase the expression of tumor suppressor proteins – p53, pRb, PTEN, and decrease markers of proliferation PCNA and Ki-67. The combination of 200 mg of indole-3-carbinol and 60 mg of trans-resveratrol for the prevention of persistent papillomavirus infection and the treatment of cervical intraepithelial neoplasia has impressive potential; however, further research is needed to determine the most effective application schemes.

An integrated approach to secondary prevention of cervical intraepithelial neoplasia

Secondary prevention of cervical precancer is aimed at preventing recurrence of cervical intraepithelial neoplasia (CIN) after excisional treatment. Recurrence of CIN after surgical treatment occurs in 8.1–14.4% of cases, which increases the risk of developing cervical cancer (CC). Despite the high effectiveness of local surgical treatment of patients with high-grade intraepithelial lesions (HSIL), an increased risk of late diagnosis of cervical cancer has been proven in comparison with the risk in the general population. The review article presents current data on factors that increase the potential risk of recurrence of precancer. Human papillomavirus (HPV) persistence is considered one of the leading predictors of relapse of CIN2+, regardless of the type of excision treatment. The combination of persistent high-risk (HR) HPV and a positive sectional margin significantly increases the risk of persistent/recurrent CIN2+. A negative co-test after conization during follow-up contributes to a favorable prognosis and the development of HSIL is observed less frequently than in the population. Only an integrated approach, including detection of cervical HPV HR infection after excisional treatment of CIN, assessment of the radicality of resection and timely measures to eliminate ineffective treatment, as well as subsequent active monitoring of patients, allows avoiding its recurrence and progression of cervical precancer

Potential mechanisms of ZiGongDing in treating HPV-induced cervical intraepithelial neoplasia: a network pharmacology and experimental verification study.

The onset of cervical intraepithelial neoplasia (CIN) is strongly associated with persistent infection caused by high-risk human papillomavirus (HPV). ZiGongDing (ZGD), a traditional Chinese medicine, has progressed to clinical application in HPV-induced CIN treatment, yet the underlying mechanism remains unclear. The objective of this paper is to explore the mechanism of ZGD in treating HPV-induced CIN by integrating a combination of network pharmacology and experimental validation. The active ingredients and targets of ZGD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. CIN-related targets were sourced from GeneCards and the Online Mendelian Inheritance in Man (OMIM) database. Protein-protein interaction (PPI) and functional enrichment analyses were conducted to determine the potential molecular mechanism. The herb-active ingredient-target network was constructed by Cytoscape software. To further validate the therapeutic mechanism, molecular docking and in vitro experiments were performed. In this study, we identified 60 active ingredients in ZGD and 46 common targets in of CIN treatment. The PPI network analysis revealed estrogen receptor 1 (ESR1) as a pivotal target in ZGD against CIN. Functional enrichment analysis showed that the estrogen signaling pathway was mostly enriched, and ESR1 was involved. The herb-active ingredient-target network and relative literature identified cnidimol B as the primary active ingredient. Molecular docking demonstrated a strong binding affinity between ESR1 and cnidimol B. Cellular experiments revealed that cnidimol B could significantly decrease the viability of HeLa and CaSki cells. Moreover, the expression of ESR1 was notably upregulated in HeLa and CaSki cells after treatment with cnidimol B. Our study proposes a novel mechanism underlying ZGD against CIN, which involves the modulation of ESR1. This insight lays a solid foundation for further exploring and optimizing ZGD's therapeutic potential.

Evaluation of Cold Conization Indications and Results

Objective: The aim of this study was to determine the efficiency and indications of cold knife conization in the treatment of high-grade cervical lesions. Materials and Methods: This study included patients with high-grade cervical lesions treated with cold knife conization (CKC) within 9 years. Histopathological correlation analyses were carried out among the smear, colposcopic biopsy (CBx), CKC results, and total hysterectomy specimens available. Results: One hundred thirty-one cold knife cone biopsy cases were analyzed for this study. The most common pathology was cervical intraepithelial neoplasia (CIN) II–III, with a frequency of 64 (48.9%). Other conization results in order of frequency were as follows: CIN I at a rate of 29 (22.1%), Carcinoma (Ca) at 19 (14.5%), cervicitis at 14 (10.7%), and negative results at 5 (3.8%). Conclusions: CKC remains an acceptable option in the treatment of CIN and microinvasive carcinoma of the cervix, and the excellent diagnostic and therapeutic efficacy of CKC is well-known and confirmed. When properly performed, the procedure has a low risk of complications and provides an accurate histological representation of the disease process. It is also curative in most cases. Of course, excellent clinical results still require careful, long-term, and attentive follow-up.

Fertility and Miscarriage Incidence After Cervical Intraepithelial Neoplasia Treatment by Thermal Ablation: A Cohort Study.

To assess the impact of thermal ablation (TA) for the treatment of cervical dysplasia on fertility and pregnancy outcomes among women screened for cervical cancer in Cameroon. Retrospective cohort study. Dschang health district, Cameroon. Participants aged 30-45 years from two screening trials conducted between 2015 and 2020 in Dschang District Hospital. Participants were primarily screened for human papillomavirus infection, triaged by visual inspection and treated by TA if needed. Between October 2021 and March 2022, interviews on subsequent fertility were conducted with participants treated by TA and a control group of untreated women. Pregnancy and miscarriage after screening/treatment. A total of 760 participants (219 treated and 541 untreated) completed the survey, with a mean follow-up time of 1297 days. Sixty-two women (28.3%) treated by TA reported a pregnancy postscreening versus 165 (30.5%) in the control group (p = 0.550). Adjusted for potential confounders, the hazard ratio of pregnancy for treated compared with untreated women was 0.82 (0.54-1.24, p = 0.350). Among women reporting pregnancies with a known outcome and which were not voluntarily terminated, 18 (35.3%) treated participants had a miscarriage versus 31 (21.4%) in the control group (p = 0.048). In the adjusted model, no association remained between TA and miscarriage (1.04, 0.39-2.78, p = 0.935). In our study population, TA did not significantly impact fertility nor miscarriage risk. Our results support the widespread use of TA as a treatment of choice for precancerous cervical lesions in low-income settings.

Intravaginal artesunate pessaries for treatment of cervical intraepithelial neoplasia 2/3 among HIV-positive and HIV-negative women in Kenya: Study protocol for a pilot trial.

Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), which bear 90% of deaths. Current precancer treatments rely on healthcare workers who may be out of reach for many women. Development of a patient-controlled cervical precancer treatment can significantly improve access in remote areas and promote secondary prevention of cervical cancer. This is a phase I trial among 18 HIV-positive and HIV-negative women in Kenya, investigating use of artesunate vaginal pessaries as treatment for cervical precancer among women screening positive for cervical precancer who need excisional treatment. The primary objective will be the safety of self-administered artesunate pessaries. Participants will self-administer 200mg of artesunate vaginally daily for 5 days, followed by a drug-free week, repeated for a total of 4 cycles (artesunate self-administration on weeks 1, 3, 5, 7). The total study duration, including participant follow-up is 48 weeks. Safety and adherence will be assessed through review of symptom diaries and biweekly follow-ups during the treatment phase. Data analysis will include quantitative and qualitative methods. Figure 1 illustrates the study schema. Considering the challenges associated with excisional treatments for cervical precancer in LMICs where access to care is limited, this study proposes an alternative approach using intravaginal Artesunate. This clinical trial will provide important safety and efficacy data on using artesunate as a topical therapy for both HIV-positive and HIV-negative women. ClinicalTrials.gov identifier: NCT06165614.

Surgical protocols for oral leukoplakia and precancerous lesions across three different anatomic sites.

This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.

Immunohistochemistry staining of Eag1 and p16/Ki-67 can help improve the management of patients with cervical intraepithelial Neoplasia after cold knife conversion

BackgroundImmunohistochemistry (IHC) is widely used in the management of patients with cervical intraepithelial neoplasia (CIN) but still has many limitations in clinical practice. We analyzed the correlation of new biomarkers with the severity of CIN and follow-up outcomes in patients after conization to improve the management of patients with CIN.MethodsIHC staining of Eag1 and p16/Ki-67 was performed on cervical tissue sections from 234 patients with suspected CIN2/3. After a series of follow-ups, including human papillomavirus (HPV) test and thinprep cytologic test (TCT) for 1–2 years, the outcomes were collected. IHC scores of biomarkers and follow-up results were used to analyze the correlation and assess the diagnostic efficiency of biomarkers.ResultsThe IHC staining intensity of Eag1 and p16/Ki-67 was significantly different from that of the CIN1-3 groups (p < 0.05). Eag1 expression scores were significantly different in the distribution between the two follow-up groups (p < 0.001). ROC curves based on the correlations between the follow-up outcomes and the Eag1 scores and IS of p16/ki-67 showed that Eag1 had a greater AUC (0.767 vs. 0.666). Logistic regression analysis of the combination of biomarkers revealed a greater AUC value than any single biomarker.ConclusionsEag1 expression was significantly correlated with CIN grade and follow-up outcomes after conization. IHC staining of combinations of biomarkers of Eag1, p16 and Ki-67 may help us to improve the ability to identify risk groups with abnormal follow-up outcomes after treatment for CIN.

Pharmacological correction of immunological disorders in perimenopausal women with recurrent epithelial cervical dysplasia associated with human papillomavirus infection

Despite the successes achieved in implementing screening programs and treating diseases caused by human papillomavirus (HPV) infection, the frequency of cervical intraepithelial neoplasia (CIN) of moderate and high grades associated with high-risk human papillomavirus (HR-HPV) remains between 9% to 21%. Vaginal dysbiosis and the development of immunodeficient states due to persistent HR-HPV infection require effective immunomodulatory and antiviral therapy before cervical surgery in perimenopausal women with recurrent CIN II.The objective: to evaluate the effectiveness of antiviral and immunomodulatory therapy by determining the state of vaginal biocenosis, immunological status and papillomavirus load of the cervical mucosa before surgical treatment in perimenopausal women with recurrent CIN II.Materials and methods. A prospective study was conducted on 98 women aged 40 to 55 years old, including 60 patients with morphologically verified recurrent CIN II associated with high-risk HPV, forming the main group. The control group comprised 38 women with negative HPV test results and without significant gynecological or somatic pathology. In the main group, a complex consisting of a blend of plant extracts of sod pike grass (Deschampsia caespitosa), ground cinquefoil grass (Calamagrostis epigeios), and echinacea purpurea grass (Echinaceae purpureae) was administered orally.Vaginal microbiota was assessed using Hey-Іson criteria, and immunological status was examined in patients using solid-phase enzyme-linked immunosorbent assay to determine IgG, IgM, IgA antibodies in serum and cervical mucus, levels of interleukin-1β (IL-1β), interferons alpha (IFN-α), gamma (IFN-γ), tumor necrosis factor alpha (TNF-α). Additionally, the DNA of high-risk HPV in cervical mucosa was quantitatively assessed using real-time PCR. The investigations were conducted before and after the applied therapy.Results. The investigation of vaginal content revealed the presence of bacterial vaginosis in 65.0% of patients in the main group, the frequency of which decreased by 2 times after treatment, with the number of women with an intermediate type of vaginal content increasing by 2.8 times (51.7%) and those with normal microbiota increasing by 2.5 times. Disruptions in cellular and humoral immunity systems were identified. After treatment, there was an increase in viral load in the significant «threshold» category (3–5 lg) by 1.25 times and in the «above threshold for progression» category (&gt;5 lg) by 2.3 times, reflecting natural HPV clearance. No direct correlation was found between viral load activity and the degree of CIN or positive morphological changes regarding regression of cervical intraepithelial lesions.Conclusions. The use of a complex containing a blend of plant extracts of sod pike grass (Deschampsia caespitosa), ground cinquefoil grass (Calamagrostis epigeios), and echinacea purpurea grass (Echinacea purpureae) improves the state of vaginal biocenosis, indicators of cellular and humoral immunity, and promotes HPV elimination, it has adequate safety and tolerability, which determines the feasibility of its use in the complex treatment of cervical intraepithelial neoplasia at the preparatory stage before surgery and in the postoperative period to prevent complications and relapses.

Comparative Study of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy and the Loop Electrosurgical Excision Procedure for the Treatment of Cervical High-Grade Squamous Intraepithelial Lesions.

The loop electrosurgical excision procedure (LEEP) is a common treatment for cervical intraepithelial neoplasia (CIN). Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) is a non-invasive modality that has been used for treating precancerous diseases and HPV infections. This comparative study evaluated the efficacy and safety of ALA PDT and the LEEP in the treatment of cervical high-grade squamous intraepithelial lesions (HSILs). Patient records were reviewed and HSIL patients with HPV infections (24-51 years old) who underwent PDT or LEEP treatment were selected. Efficacy was analyzed blindly based on HPV-DNA, cytology, and colposcopy-directed biopsy obtained at 6 months after treatment. Treatment-related discomfort and side effects were also analyzed. Cure rates of 88.1% and 70.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. HPV-negative conversion rates of 81.0% and 62.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. The overall lesion remission rate of the PDT group was 19% higher than that of the LEEP group. The incidence of side effects was much lower in the PDT group. These results show that ALA PDT is a feasible non-invasive treatment for cervical HSIL.

Prognostic outcome of cervical laser ablation using a holmium yttrium-aluminum-garnet (Ho:YAG) laser for the treatment of cervical intraepithelial neoplasia: A single-center retrospective study

ObjectiveAlthough cervical conization is considered a standard treatment for cervical intraepithelial neoplasia (CIN) 2/3, laser ablation can compensate for the disadvantages of the former. CO2, semiconductor, and holmium yttrium-aluminum-garnet (Ho:YAG) lasers are applied in ablation, but no previous studies have shown the effectiveness of any of these techniques. Here, we retrospectively analyzed the application of the Ho:YAG laser in our hospital to verify its efficacy, and discussed the methods for optimal recurrence detection. MethodsWe evaluated the recurrence rates of the pathological condition in patients who underwent laser ablation with a Ho:YAG laser for CIN2/3 at our institution from June 2012 to November 2021. We defined the recurrence as histologically confirmed CIN2 or more advanced stage. Age, preoperative diagnosis, human papillomavirus (HPV) genotype, and postoperative high-risk HPV status were recorded to establish their association with recurrence rates. ResultsWe performed surgery in 607 patients and the 2-year recurrence rate after interventions was 5.6%. Five patients were diagnosed with invasive cancer at the time of recurrence. Older age significantly correlated with higher risk of recurrence, but preoperative CIN grade and preoperative HPV 16/18 status did not significantly affect it. The postoperative high-risk HPV test was 100% sensitive for detecting recurrence. ConclusionsLaser ablation with the Ho:YAG laser yields promising results. Together with postinterventional management, high-risk HPV test after laser ablation should be conducted after diagnostic conization.This study received the approval from the Ethics Committee of the NHO Tokyo Medical Center (Ethics Committee approval number: R22-067).

The Impact of Diagnosis of Human Papillomavirus (HPV) Infection and Electrosurgical Excision Procedure (LEEP) for Cervical Intraepithelial Neoplasia 3 (CIN3) on Women's Sexual Lives.

The aim of the study was to assess sexual health in women who underwent Loop Electrosurgical Excisional Procedure (LEEP) for the treatment of cervical intraepithelial neoplasia 3 (CIN 3). One hundred thirty-one women were enrolled, and the Female Sexual Function Index (FSFI) questionnaire was administered before LEEP and 6 months after the procedure. In almost all of the participants, data revealed a statistically significant worsening in sexual quality of life after LEEP. Therefore, clinicians should be aware of these possible negative effects on sexual behavior, and provide women with appropriate, wide-ranging, and detailed counseling. The data obtained in the present study should help to plan appropriate counseling from communicating HPV diagnosis and medical treatment to CIN3 surgical procedure.

Treatment methods for cervical intraepithelial neoplasia in England: A cost-effectiveness analysis.

To compare the cost-effectiveness of different treatments for cervical intraepithelial neoplasia (CIN). A cost-effectiveness analysis based on data available in the literature and expert opinion. England. Women treated for CIN. We developed a decision-analytic model to simulate the clinical course of 1000 women who received local treatment for CIN and were followed up for 10 years after treatment. In the model we considered surgical complications as well as oncological and reproductive outcomes over the 10-year period. The costs calculated were those incurred by the National Health Service (NHS) of England. Cost per one CIN2+ recurrence averted (oncological outcome); cost per one preterm birth averted (reproductive outcome); overall cost per one adverse oncological or reproductive outcome averted. For young women of reproductive age, large loop excision of the transformation zone (LLETZ) was the most cost-effective treatment overall at all willingness-to-pay thresholds. For postmenopausal women, LLETZ remained the most cost-effective treatment up to a threshold of £31,500, but laser conisation became the most cost-effective treatment above that threshold. LLETZ is the most cost-effective treatment for both younger and older women. However, for older women, more radical excision with laser conisation could also be considered if the NHS is willing to spend more than £31,500 to avert one CIN2+ recurrence.

Comparing two photodynamic therapy protocols for high-grade cervical intraepithelial neoplasia

SignificancePhotodynamic therapy (PDT) is a therapeutical modality which offers a minimally invasive alternative for high-grade cervical intraepithelial neoplasia (CIN) treatment. Approachthis prospective randomized controlled clinical trial aims to compare two PDT protocols for histopathologically similar high-grade CIN treatment. In protocol 1, only ectocervix is treated; in protocol 2, the patients had both the ectocervix and endocervix illuminated simultaneously with LED plus LASER (a cylindrical diffuser fiber was coupled inside the squamocolumnar junction). In both groups was applied 20% MAL overnight and the irradiance delivered was 120 mW/cm2, for 21 minutes, in a fluency rate of 150 J/cm2. Resultsafter two years of follow-up, group 1 showed 96% cure and group 2, 87%. Conclusionsno significant difference was observed between the two protocols. However, the number of patients who completed the two-year follow-up is still low and we expect better conclusions with more patients followed.

Diagnosis and Management of Cervical Squamous Intraepithelial Lesions in Pregnancy and Postpartum.

Perinatal care provides important health care opportunities for many individuals at risk for cervical cancer. Pregnancy does not alter cervical cancer screening regimens. ASCCP risk-based management has a colposcopy threshold of a 4% immediate risk of cervical intraepithelial neoplasia (CIN) 3 or cancer, but the actual risk can be considerably higher based on current and past screening results. Improving cervical cancer outcomes with diagnosis during pregnancy rather than postpartum and facilitating further evaluation and treatment postpartum for lesser lesions are the perinatal management goals. Although colposcopy indications are unchanged in pregnancy, some individuals with lower risk of CIN 2-3 and reliable access to postpartum evaluation may defer colposcopy until after delivery. Cervical intraepithelial neoplasia diagnosed in pregnancy tends to be stable, with frequent regression postpartum, though this is not universal. Colposcopic inspection during pregnancy can be challenging. Although biopsies in pregnancy are subjectively associated with increased bleeding, they do not increase complications. Endocervical curettage and expedited treatment are unacceptable. Treatment of CIN 2-3 in pregnancy is not recommended. Excisional biopsies in pregnancy are reserved for suspicion of malignancy that cannot be confirmed by colposcopic biopsy and when excisional biopsy results would alter oncologic or pregnancy care. Surveillance of high-grade lesions in pregnancy uses human papillomavirus-based testing, cytology, and colposcopy, with biopsy of worsening lesions every 12-24 weeks from diagnosis until postpartum evaluation. Mode of delivery does not definitively affect persistence of CIN postpartum. Postpartum care may involve a full colposcopic evaluation or expedited excisional procedure if indicated.

YAP/TAZ-TEAD activity promotes the malignant transformation of cervical intraepithelial neoplasia through enhancing the characteristics and Warburg effect of cancer stem cells

A number of studies have confirmed that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)-transcriptional enhanced associate domain (TEAD) activity is the driver of cancer development. However, the role and mechanism of the YAP/TAZ-TEAD pathway in cervical intraepithelial neoplasia (CIN) remain to be clarified. Therefore, this study was designed to observe the effect of YAP/TAZ-TEAD activity on the development of CIN and provide new ideas for the diagnosis and treatment of CIN. Firstly, cervical tissues were collected from CIN patients in different stages [CIN grade 1 (CIN1) tissue, CIN grade 2/3 (CIN 2/3) and squamous cell carcinoma (SCC)] and healthy volunteers. Next, the expression levels of YAP, TAZ and TEAD in cervical tissues and cells were observed by immunohistochemistry, qRT-PCR and western blot. Besides, Z172 and Z183 cells were transfected with siRNA-YAP/TAZ (si-YAP/TAZ) and YAP/TAZ overexpression vector (YAP-5SA). Also, Z172 cells were co-transfected with YAP-5SA and si-TEAD2/4. Subsequently, the stemness characteristics, glycolysis level and malignant transformation of cells in each group were observed by sphere-formation assay, commercial kit, MTT, Transwell, scratch experiment, xenotransplantation and western blot.The expression of YAP, TAZ and TEAD increased significantly in cervical cancer tissue and cell line at the stage of CIN2/3 and SCC. When YAP/TAZ was knocked down, the stemness characteristics, glycolysis level and malignant transformation of cancer cells were notably inhibited; while activating YAP/TAZ exhibited a completely opposite result. In addition, activating YAP/TAZ and knocking down the TEAD expression at the same time significant weakened the effect of activated YAP/TAZ signal on precancerous cells and reduced inhibitory effect of knocking down TEAD alone. YAP/TAZ-TEAD signal activates the characteristics and Warburg effect of cancer stem cells, thereby promoting the malignant transformation of CIN.

Modulation of sHLA-G, PD-1, and PD-L1 Expression in Cervical Lesions Following Imiquimod Treatment and Its Association with Treatment Success.

(1) Background: Cervical intraepithelial neoplasia (CIN) is a precancerous condition linked to human papillomavirus (HPV) infection, often necessitating surgical interventions carrying the risk of subsequent preterm births. This study explores the potential of imiquimod (IMQ), as a non-invasive alternative treatment. The focus is on understanding IMQ impact on immune checkpoint molecules, particularly PD-1, PD-L1, and sHLA-G, which play pivotal roles in shaping immune responses and cancer progression. (2) Methods: Forty-three patients diagnosed with a high-risk squamous intraepithelial lesion (HSIL, p16-positive) self-applied 5% IMQ encapsulated in sachets containing 250 g of cream into the vaginal cavity three times a week for 16 weeks. The impact of IMQ therapy on cervical lesion regression was assessed through immunohistochemistry (IHC), examining changes in sHLA-G, PD-L1, and PD-1 levels. The antiviral activity of IMQ was evaluated through HPV-E7 immunofluorescence. Ethical considerations were adhered to, and the research methods were based on a previously approved clinical trial (clinicaltrials.gov Identifier: NCT04859361). (3) Results: IMQ treatment demonstrated efficacy, leading to lesion regression. sHLA-G levels in CIN before starting IMQ application were associated with unsuccessful treatment (p = 0.0036). IMQ did not significantly alter the expression of PD-1. We observed a decrease in PD-L1 levels in those who were successfully treated (p = 0.0509) and a reduction in HPV burden. (4) Conclusions: IMQ exhibits promise as a non-invasive treatment for CIN, emphasising its potential to modulate the immune microenvironment. Baseline sHLA-G levels emerge as potential predictors of treatment response. Understanding the nuanced dynamics of immune checkpoints sheds light on IMQ mechanism of action. Further exploration is warranted to decipher the intricate mechanisms underlying IMQ treatment in the context of cervical lesions.

In-clinic Versus Online Recruitment of Women With a History of Cervical Intraepithelial Neoplasia or Cervical Cancer to a Smoking Cessation Trial: A Post hoc Comparison of Participant Characteristics, Study Retention, and Cessation Outcomes.

Recruiting special populations to smoking cessation trials is challenging and approaches beyond in-clinic recruitment may be beneficial. This secondary analysis of data from a smoking cessation RCT for individuals with a history of cervical cancer or cervical intraepithelial neoplasia (CIN) explored differences associated with in-clinic vs. online recruitment. Participants were recruited from clinics within a university-based NCI-designated cancer center (n = 87) and online nationally via Facebook (n = 115). Baseline measures included sociodemographics, smoking history, and cancer or CIN history. Study retention and smoking abstinence were assessed 12 months post-baseline. Group differences in baseline characteristics were evaluated. Retention and abstinence were evaluated while controlling for group differences and predictors. Participants recruited online (vs. in-clinic) had higher educational attainment (p = .01) and health literacy (p = .003). They were more likely to have CIN versus cancer, to be further from the time of diagnosis, and to have completed active treatment (p values < .001). While controlling for these group differences and independent predictors, retention was higher among participants recruited online (log-likelihood χ2(1) = 11.41, p < .001). There were no recruitment differences in self-reported (p = .90) or biochemically confirmed smoking abstinence (p = .18). Compared to individuals recruited in-person, individuals recruited online were more educated, had higher health literacy, and presented with a different clinical profile (ie, more likely to have CIN vs. cancer and to have completed active treatment). There were few differences in participant characteristics between recruitment approaches, and no differences on any smoking-related variables. Online recruitment has the potential to improve enrollment of cancer survivors in smoking cessation trials. People with a history of CIN or cervical cancer recruited to a smoking cessation RCT online (vs. in-clinic) were more likely to have a diagnosis of CIN versus cancer and were more educated and health literate. Participants recruited online were more likely to be retained in the study and there were no differences in smoking abstinence rates at 12 months. Incorporating online recruitment increased the reach of tobacco treatment efforts to a larger and more diverse sample. This could reduce the burden of tobacco-related disease, improve CIN and cancer treatment outcomes, and reduce secondary malignancies and morbidity among this underserved group.

Performance of Different Follow-Up Strategies and Genotype-Based Recurrence Risk After Treatment of Cervical High-Grade Squamous Intraepithelial Lesion.

Our aim was to evaluate the performance of different follow-up strategies after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3, including human papillomavirus (HPV) detection, cytology, or colposcopy, as well as their combinations. Additionally, we compared the influence of the persistence of HPV 16/18 versus that of other high-risk HPV genotypes (HR-HPV) in the recurrence risk. Retrospective register-based study, including women who had an excision of the transformation zone for CIN2 or CIN3 at our institution, between January 2011 and December 2022. The outcome assessed was histopathological recurrence/persistence of CIN2 or worse. Of the 721 women included, 6.8% (49/721) had recurrence/persistence. The sensitivity, specificity, and positive and negative predictive values of the HPV test were 97.4%, 80%, 22.3%, and 99.8%, respectively, whereas for cotesting (HR-HPV and cytology), 86.8%, 90.1%, 34.4%, and 99.1%, respectively. The referral rates for colposcopy were 24.3% and 14.2%, respectively. The sensitivity of colposcopy was low (40.0%).Women who were initially positive for non-16/18 genotypes at baseline who became HPV16/18 positive during follow-up, had a statistically significant increased risk of CIN2 or worse, compared with those who tested positive only for other HR-HPV genotypes during both stages (hazard ratio = 4.98; 95% CI = 1.66-14.91). Human papillomavirus testing is the best strategy for follow-up after treatment of cervical HSIL. The addition of cytology triage decreases by more than 40% the referrals for colposcopy, without significantly missing cases of recurrence/persistence. Human papillomavirus 16/18 in the follow-up, regardless of being previously positive, is associated with higher risk of recurrence/persistence of HSIL.

Topical imiquimod cream for the treatment of cervical intraepithelial neoplasia

Topical imiquimod cream for the treatment of cervical intraepithelial neoplasia